The mammalian bombesin (Bn)-related peptides, gastrin-releasing peptide (GRP), neuromedin B (NMB), and neuromedin C (NMC) have a wide range of biological effects. These include chemotaxis, contraction of smooth muscle stimulation, and the release of numerous gastrointestinal hormones. GRP and NMB are also active in the central nervous system, affecting thermoregulation, behavioral effects, satiety, maintenance of circadian rhythm, and inhibition of TSH release. Bn-related peptides function as a growth factor in numerous normal cells (e.g., stomal, epithelial, and neuroendocrine cells) as well as neoplastic cells such as human small cell lung cancer cells, non-small cell lung cancer cells, rat hepatocellular tumor cells, prostatic cells and breast adenocarcinoma cells.
Recent structure and cloning studies demonstrate that Bn-related peptides mediate the actions of two distinct receptor classes. GRP has a high affinity, and NMB has a low affinity, for the GRP-preferring class or subtype (GRP receptor or GRP-R). In contrast, GRP has a low affinity, and NMB has a high affinity, for the other class, the NMB-preferring subtype (NMB receptor or NMB-R). Both receptor classes are present throughout the central nervous system and the gastrointestinal tract.
Native somatostatin, somatostatin-14 (SS-14), has been shown to inhibit the cross-linking of .sup.125 I-GRP to a 120 kD protein in Triton.RTM. extracts of 3T3 cells and human small cell lung cancer cells which are known to possess bombesin receptors. Recently, somatostatin octapeptide analogs have also demonstrated binding affinity to NMB-R in Orbuch, et al., Mol. Pharmacol., 44:841 (1993). These analogs, however, also maintain a substantial activity for somatostatin receptors.